Formulations based on pullulan and a derivative as coating material for the food sector.

Carboxymethylated derivatives of pullulan (PU) were synthesized and evaluated as coating for the postharvest preservation of blueberries. Carboxymethylpullulan was obtained by etherification reaction with the substitution degrees of 0.52, 0.34, and 0.26 for CMP1, CMP2, and CMP3 respectively. Infrared spectroscopy and nuclear magnetic resonance results showed characteristic signals of the carbonyl group belonging to the carboxymethyl group. Thermal analysis showed that CMP1, CMP2, and CMP3 derivatives presented thermal stability values of 209.91 C, 214.73 C, and 225.52 °C, respectively, and were lower with respect to PU with Td of 238.84 °C. Furthermore, an increase in the glass transition temperature due to carboxymethylation was determined. The chemical modification decreased the contact angle with respect to PU (71.34°) with values for CMP1, CMP2, and CMP3 of 39.89°, 53.72° and 60.61°, respectively. The carboxymethylation also increased the water vapor permeability and mechanical properties of the films. In addition, it was found that the CMP molecules affected the optical properties. The application of CMP-based coatings reduced the mass loss and ripening rate of blueberries compared to native pullulan, therefore, packaging from CMP molecules could be used as a coating capable of delaying ripening and extending the shelf life of fruits.

Production and applications of pullulan from lignocellulosic biomass: Challenges and perspectives.

Pullulan is an exopolysaccharide produced by Aureobasidium pullulans, with interesting characteristics which lead to its application in industries such as pharmaceuticals, cosmetics, food, and others. To reduce production costs for industrial applications, cheaper raw materials such as lignocellulosic biomass can be utilized as a carbon and nutrient source for the microbial process. In this study, a comprehensive and critical review was conducted, encompassing the pullulan production process and the key influential variables. The main properties of the biopolymer were presented, and different applications were discussed. Subsequently, the utilization of lignocellulosics for pullulan production within the framework of a biorefinery concept was explored, considering the main published works that deal with materials such as sugarcane bagasse, rice husk, corn straw, and corn cob. Next, the main challenges and future prospects in this research area were highlighted, indicating the key strategies to favor the industrial production of pullulan from lignocellulosic biomasses.

Novel Pullulan/Gellan Gum Bilayer Film as a Vehicle for Silibinin-Loaded Nanocapsules in the Topical Treatment of Atopic Dermatitis.

In this study a novel gellan gum/pullulan bilayer film containing silibinin-loaded nanocapsules was developed for topical treatment of atopic dermatitis (AD). The bilayer films were produced by applying a pullulan layer on a gellan gum layer incorporated with silibinin nanocapsules by two-step solvent casting method. The bilayer formation was confirmed by microscopic analysis. In vitro studies showed that pullulan imparts bioadhesitvity for the films and the presence of nanocapsules increased their occlusion factor almost 2-fold. Besides, the nano-based film presented a slow silibinin release and high affinity for cutaneous tissue. Moreover, this film presented high scavenger capacity and non-hemolytic property. In the in vivo study, interestingly, the treatments with vehicle film attenuated the scratching behavior and the ear edema in mice induced by 2,4-dinitrochlorobenzene (DNCB). However, the nano-based film containing silibinin modulated the inflammatory and oxidative parameters in a similar or more pronounced way than silibinin solution and vehicle film, as well as than hydrocortisone, a classical treatment of AD. In conclusion, these data suggest that itself gellan gum/pullulan bilayer film might attenuate the effects induced by DNCB, acting together with silibinin-loaded nanocapsules, which protected the skin from oxidative damage, improving the therapeutic effect in this AD-model.

A novel nanotechnological mucoadhesive and fast-dissolving film for vaginal delivery of clotrimazole: design, characterization, and in vitro antifungal action.

Pullulan (PUL) films containing pomegranate seed oil and Eudragit® RS100 nanocapsules loaded with clotrimazole (CTZ-NC-PUL) were developed to treat vulvovaginal candidiasis (VVC). Our findings showed that the nanocapsule average diameter was around 163 ± 4 nm, with polydispersity index values of up to 0.1 ± 0.01 and positively charged zeta potential (+ 43.5 ± 0.7 mV). The pH was in the acid range (5.14 ± 0.12) and encapsulation efficiency was around 99.6%; CTZ nanoencapsulation promoted higher homogeneity values for the film (91%), and the stability studies displayed no changes in the drug content after 120 days for the CTZ-NC-PUL under refrigerated conditions. All formulations were considered non-irritant, and CTZ-NC-PUL promoted a controlled release of the drug (60% in 24 h) compared to CTZ-PUL (100% in 8 h). The permeation results corroborate the drug release, where higher CTZ amounts were found in the mucosa and receptor medium for CTZ-PUL (21.02 and 4.46 µg/cm2). The films were fast dissolving (10 min), and CTZ-NC-PUL presented higher mucoadhesive properties; the antifungal activity against Candida albicans was maintained, and the in vitro efficacy of the film was proved. In conclusion, CTZ-NC-PUL formulation was considered promising and suitable for vaginal application against candida-related infections.

Chemical Modification of Pullulan Exopolysaccharide by Grafting Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBHV) via Click Chemistry.

Biodegradable and biocompatible copolymers have been often studied for the development of biomaterials for drug delivery systems. In this context, this work reports the synthesis and characterization of a novel pullulan-g-poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (Pull-g-PHBHV) graft copolymer using click chemistry. Well-defined and functional pullulan backbones containing azide groups (PullN3) previously prepared by our group were successfully used for this purpose and propargyl-terminated poly(3-hydroxybutyrate-co-3-hydroxyvalerate) was prepared via transesterification using propargyl alcohol as a chain transfer agent. By an alkyne-azide cycloaddition reaction catalyzed by copper (Cu (I)) (CuAAC), the graft copolymer Pull-g-PHBHV was obtained. The chemical structures of the polymers were accessed by 1H NMR and 13C NMR FTIR. Disappearance of the bands referring to the main bonds evidenced success in the grafting reaction. Besides that, DRX, DSC and TGA were used in order to access the changes in crystallinity and thermal behavior of the material. The remaining crystallinity of the Pull-g-PHBHV structure evidences the presence of PHBHV. Pull-g-PHBHV presented lower degradation maximum temperature values than the starting materials, indicating its minor thermal stability. Finally, the synthesized material is an innovative biopolymer, which has never been reported in the previous literature. It is a bio-derived and biodegradable polymer, chemically modified, resulting in interesting properties which can be useful for their further applications as biomedical systems for controlled delivery, for example.

Taste-masked nanoparticles containing Saquinavir for pediatric oral administration.

This research has aimed to improve the stability and taste-masking properties by developing nanostructured dosage forms containing Saquinavir. Liquid formulations were developed using Eudragit RS100® and Pullulan as polymers. The physicochemical characteristics, stability, in vitro drug release, morphology, mucoadhesion and taste masking capacity were evaluated. The Saquinavir-nanoparticles had average diameters between 136 and 158 nm, with a Span below 1.4. These formulations presented a drug content above 80%, a high encapsulation efficiency (>97%), slightly acidic pH levels, low dynamic viscosity and controlled drug release. Electron microscopy revealed irregular spherical nanoparticles. The formulations prepared with higher amounts of Eudragit RS100® had greater mucoadhesion. Both polymers were able to improve drug stabilization, taste-masking properties and protection against drug cytotoxicity. The Saquinavir-nanoparticles exhibited stability and control releasing properties, thus making it a promising liquid dosage form with taste-masking properties intended for application in pediatric treatment.

Synergy between surfactants and mucoadhesive polymers enhances the transbuccal permeation of local anesthetics from freeze-dried tablets.

We report on the advance of freeze-dried mucoadhesive orodispersible tablets (ODTs) loaded with prilocaine (PRC) and lidocaine (LDC) hydrochlorides, aiming to promote noninvasive buccal anesthesia. The influences of combining biocompatible polymers (pullulan and HPMC K100 LV) and a blend of surfactants (oleic acid, polysorbate 80 and propylene glycol) acting as chemical enhancers on the permeation of such drugs through the esophageal porcine epithelium and in vitro mucoadhesion were investigated. The ODTs were also characterized in terms of average weight, thickness, pH, drug content, in vitro release, thermal behavior and scanning electronic microscopy. A dissolution test showed fast drug release within one hour. The drug release data for all ODTs fitted first order. No significant influence of the type of mucoadhesive polymer on release was observed, while the drug release from ODTs decreased in the presence of chemical enhancers. For the ODT containing pullulan the drug release mechanism was anomalous transport, whist for all others it was case-II transport. A remarkable synergic effect between pullulan and chemical enhancers on the permeation flux, lag time, and permeability coefficient of both drugs, but mainly for PRC was observed. Pullulan together with permeation enhancers also substantially improved the work of mucoadhesion as compared to HPMC. In contrast, HPMC improved drug retention in the epithelium. The novel drug delivery platform achieved by combining a freeze-drying technique, mucoadhesive biocompatible polymers, and chemical permeation enhancers displayed an effective strategy for the transbuccal delivery of PRC and LDC that can be used to improve needle-free buccal anesthesia.

Desenvolvimento e avaliação de nova preparação de anfotericina B e/ou cetoconazol em dispersão de bixina, pullulan e trealose / Development and evaluation of novel preparation of amphotericin B and/or ketoconazole in dispersion of bixin, pullulan and trehalose

Muitos pacientes acometidos por infecções fúngicas sucumbem devido a não eficácia dos antibióticos ou por toxicidade dos mesmos. Anfotericina B é um dos antifúngicos mais eficientes do mercado apesar de sua alta toxicidade, tem estrutura poliênica e é um composto insolúvel em água, sendo necessário o uso de adjuvantes e novas tecnologias para preparo de formulações eficazes. Cetoconazol é um composto imidazólico, também com ação antifúngica de grande espectro de ação e difícil solubilização em meio aquouso, porém solúvel somente em baixos valores de pH. Estudos têm demonstrado a utilização de bixina na preparação de dispersões aquosas de compostos insolúveis ou pouco solúveis em água. Bixina é o principal composto das cascas de semente de Bixa orellana (urucum), sendo um carotenoide insolúvel em água, porém, permite preparações na forma de nanodispersões aquosas com incorporação de fármacos apolares ou lipofílicos. O objetivo deste trabalho foi preparar anfotericina B e cetoconazol na forma de nanodispersões a partir de bixina, utilizando pullulan e trealose como adjuvantes e avaliar estabilidade e eficácia antimicrobiana por ensaios físico-químicos e microbiológicos. Pullulan é um polissacarídeo constituído por unidades de maltotriose, com propriedades adesivas e capacidade de formar biofilmes, enquanto trealose é um composto com duas unidades de glicose, com boa estabilidade em faixas de pH de 3 a 10 e capaz de suportar altas temperaturas, como processos de esterilização por calor úmido. Ensaios físico-químicos demonstraram boa manutenção das características das preparações propostas neste projeto, como, por exemplo, diâmetro hidrodinâmico e potencial zeta das estruturas das nanodispersões de bixina e antifúngicos e também eficácia antimicrobiana frente a Candida albicans ATCC 10231. Os resultados apresentam perspectivas para aprimoramentos de formulações com fármacos pouco solúveis ou insolúveis em água, pesquisa de novos biomateriais e outras aplicações nas áreas farmacêutica e cosmética

Many patients with fungal infections succumb due to ineffectiveness or toxicity of antibiotics. Amphotericin B is one of the most efficient antifungals on the market despite its high toxicity. It presents polyenic structure and is a water-insoluble compound. In this case, it is necessary to use adjuvants and new technologies to prepare effective formulations. Ketoconazole is an imidazolic compound, also with broad spectrum antifungal action and difficult solubilization in aqueous medium but it is soluble at low pH values. Studies have demonstrated the use of bixin in the preparation of aqueous dispersions of insoluble or poorly soluble compounds in water. Bixin is the main compound of Bixa orellana (annatto) seed husks, being a water-insoluble carotenoid, but it allows preparations in the form of aqueous nanodispersions with incorporation of apolar or lipophilic drugs. The objective of this work was to prepare amphotericin B and ketoconazole as nanodispersions from bixin, using pullulan and trehalose as adjuvants and to evaluate them under aspects of stability and efficacy by physicochemical and microbiological assays. Pullulan is a polysaccharide consisting of maltotriose units with adhesive properties and ability to form biofilms, while trehalose is a compound with two glucose units with good stability at pH ranges from 3 to 10 and capable of withstanding high temperatures such as processes of sterilization by moist heat. Physicochemical tests demonstrated good maintenance of the characteristics of the preparations proposed in this project, such as hydrodynamic diameter and zeta potential of bixin and antifungal nanodispersions and also antimicrobial efficacy against Candida albicans ATCC 10231. The results present prospects for improvement. of poorly soluble or water-insoluble drug formulations, research on new biomaterials and other applications in the pharmaceutical and cosmetic fields

Platelet lysate loaded electrospun scaffolds: Effect of nanofiber types on wound healing.

In healthy individuals, wound healing is a highly efficient process. However, interruptions of normal healing give rise to chronic wounds, characterized by inflammation with impaired angiogenesis and re-epithelialization. The aim of this work was the design and the development of electrospun nanofibrous scaffolds based on sodium alginate (SA) and pullulan (PUL) and loaded with human platelet lysate (PL) intended for skin reparation, to take the advantage of nanofibrous scaffolds (with improved physical structure) and of SA as biopolymer. Two preparation approaches have been used to load PL in the scaffolds: as component of the PUL/SA matrix, to be electrospun, or as coating component, to cover the previously prepared electrospun PUL based membranes. A preformulation study to assess pullulan entanglement concentration and alginate or citric acid critical concentration, to obtain electrospun nanofibers, has been performed. The preparation process allowed to obtain insoluble systems starting from aqueous solutions and these were able to act as scaffolds for tissue engineering with suitable mechanical properties and PL release. PL loading in PUL/SA matrix nanofibers did not substantially modify the nanofiber morphology before crosslinking, while the crosslinking process, in presence of PL, determined less sharp nanofibers probably due to an increase in hydrophilicity caused by PL proteins. On the contrary, the coated nanofibers showed an increase in diameters due to PL loading. The two different approaches affected the fiber dimension and scaffold elasticity, especially for PL loaded systems. Anyhow, these differences were not crucial for fibroblast adhesion and proliferation which were mainly influenced by PL loading. In particular, fibroblasts presented different conformation and orientation mainly due to the presence of PL. This caused a cell random orientation compatible to a fibroblast-to-myofibroblast transition that could enhance wound healing.

Efficient production of pullulan by Aureobasidium pullulans grown on mixtures of potato starch hydrolysate and sucrose

Abstract Pullulan is a natural exopolysaccharide with many useful characteristics. However, pullulan is more costly than other exopolysaccharides, which limits its effective application. The purpose of this study was to adopt a novel mixed-sugar strategy for maximizing pullulan production, mainly using potato starch hydrolysate as a low-cost substrate for liquid-state fermentation by Aureobasidium pullulans. Based on fermentation kinetics evaluation of pullulan production by A. pullulans 201253, the pullulan production rate of A. pullulans with mixtures of potato starch hydrolysate and sucrose (potato starch hydrolysate:sucrose = 80:20) was 0.212 h−1, which was significantly higher than those of potato starch hydrolysate alone (0.146 h−1) and mixtures of potato starch hydrolysate, glucose, and fructose (potato starch hydrolysate:glucose:fructose = 80:10:10, 0.166 h−1) with 100 g L−1 total carbon source. The results suggest that mixtures of potato starch hydrolysate and sucrose could promote pullulan synthesis and possibly that a small amount of sucrose stimulated the enzyme responsible for pullulan synthesis and promoted effective potato starch hydrolysate conversion effectively. Thus, mixed sugars in potato starch hydrolysate and sucrose fermentation might be a promising alternative for the economical production of pullulan.

Efficient production of pullulan by Aureobasidium pullulans grown on mixtures of potato starch hydrolysate and sucrose

Pullulan is a natural exopolysaccharide with many useful characteristics. However, pullulan is more costly than other exopolysaccharides, which limits its effective application. The purpose of this study was to adopt a novel mixed-sugar strategy for maximizing pullulan production, mainly using potato starch hydrolysate as a low-cost substrate for liquid-state fermentation by Aureobasidium pullulans. Based on fermentation kinetics evaluation of pullulan production by A. pullulans 201253, the pullulan production rate of A. pullulans with mixtures of potato starch hydrolysate and sucrose (potato starch hydrolysate:sucrose = 80:20) was 0.212 h-¹, which was significantly higher than those of potato starch hydrolysate alone (0.146 h-¹) and mixtures of potato starch hydrolysate, glucose, and fructose (potato starch hydrolysate:glucose:fructose = 80:10:10, 0.166 h-¹) with 100 g L-¹ total carbon source. The results suggest that mixtures of potato starch hydrolysate and sucrose could promote pullulan synthesis and possibly that a small amount of sucrose stimulated the enzyme responsible for pullulan synthesis and promoted effective potato starch hydrolysate conversion effectively. Thus, mixed sugars in potato starch hydrolysate and sucrose fermentation might be a promising alternative for the economical production of pullulan.(AU)

An innovative polysaccharide nanobased nail formulation for improvement of onychomycosis treatment.

Tioconazole-loaded nanocapsule suspensions and its coating with a cationic polymer were developed for nail drug delivery. The colloidal systems presented a nanometric size around 155nm for uncoated nanoparticles and 162nm for those with the cationic coating, with negative and positive zeta potential values, respectively. Both nanosuspensions showed drug content close to theoretical values (1mgmL-1), association efficiency close to 100% (HPLC) and were able to control tioconazol release. The developed formulations showed in vitro antifungal activity (agar diffusion method) against C. albicans. The cationic nanocapsules were considered bioadhesive, showed higher viscosity and were chosen to be incorporated into an ungueal formulation. Pullulan nanobased nail formulation showed adequate viscosity for nail application and drug content close to the theoretical values. It was equivalent to the commercial formulation Trosid® in preventing nail infection by T. rubrum in an in vitro onychomycosis model. The nanocapsule suspensions and Pullulan nanobased nail formulation showed lower irritant potential than the commercial formulation and than free drug in an in vitro evaluation. Pullulan nanobased nail formulation is promising for the treatment of onychomycosis.

Efficient production of pullulan by Aureobasidium pullulans grown on mixtures of potato starch hydrolysate and sucrose.

Pullulan is a natural exopolysaccharide with many useful characteristics. However, pullulan is more costly than other exopolysaccharides, which limits its effective application. The purpose of this study was to adopt a novel mixed-sugar strategy for maximizing pullulan production, mainly using potato starch hydrolysate as a low-cost substrate for liquid-state fermentation by Aureobasidium pullulans. Based on fermentation kinetics evaluation of pullulan production by A. pullulans 201253, the pullulan production rate of A. pullulans with mixtures of potato starch hydrolysate and sucrose (potato starch hydrolysate:sucrose=80:20) was 0.212h-1, which was significantly higher than those of potato starch hydrolysate alone (0.146h-1) and mixtures of potato starch hydrolysate, glucose, and fructose (potato starch hydrolysate:glucose:fructose=80:10:10, 0.166h-1) with 100gL-1 total carbon source. The results suggest that mixtures of potato starch hydrolysate and sucrose could promote pullulan synthesis and possibly that a small amount of sucrose stimulated the enzyme responsible for pullulan synthesis and promoted effective potato starch hydrolysate conversion effectively. Thus, mixed sugars in potato starch hydrolysate and sucrose fermentation might be a promising alternative for the economical production of pullulan.

Pullulan as a stabilizer agent of polymeric nanocapsules for drug delivery

ABSTRACT Polymeric stabilizers have received attention in the preparation of nanostructured systems due to their ability to enhance formulation stability. Considering this, the objective of this work was to prepare poly(ε-caprolactone) nanocapsules using the pullulan as a polymeric stabilizer. The nanocapsules were prepared using the interfacial deposition method of preformed polymers and they were characterized in terms of pH, average diameter, polydispersity index, zeta potential, beclomethasone dipropionate content, encapsulation efficiency, photostability and drug release profiles. The formulations showed physicochemical characteristics consistent with nanocarriers for drug delivery such as: average diameter lower than 270 nm, polydispersity indexes lower than 0.2, negative zeta potential (-22.7 to -26.3 mV) and encapsulation efficiencies close to 100%. In addition, the nanocapsules were able to delay the beclomethasone dipropionate photodegradation under UVC radiation and by the dialysis bag diffusion technique, the nanocapsules were able to prolong the drug release. Thus, pullulan could be considered an interesting excipient to formulate polymeric nanocapsules.

Diseño de un sistema bioadhesivo de clorhexidina empleando pullulan como matriz para uso en mucosa oral / Design of a bioadhesive system with chlorhexidine using pullulan as matrix for use in oral mucous

Se desarrollaron sistemas poliméricos bioadhesivos del tipo película polimérica y comprimido empleando el biopolímero pullulan, para el transporte de digluconato de clorhexidina, el cual es un principio activo utilizado como alternativa terapéutica en el tratamiento de la gingivitis y de la enfermedad periodontal. Inicialmente, se evaluó la capacidad del polímero para formar películas y tabletas, luego, fueron propuestas formulaciones de cada uno de los sistemas. A las películas y comprimidos obtenidos se les determinaron propiedades mecánicas y de transporte, actividad antiséptica, caracterización de las microestructuras obtenidas, además, se comprobó la liberación del fármaco desde los sistemas estudiados. Con las formulaciones seleccionadas se determinó su capacidad mucoadhesiva in vitro, empleando como sustrato mucosa oral porcina.

As a therapeutic alternative in the transport of active substances in treatment of gingivitis and periodontal disease, bioadhesive polymeric systems type polymeric film and tablet were developed using the biopolymer pullulan. First, the ability of pullulan polymer to form films and tablets was evaluated and formulations were proposed for each system. Mechanical and transport properties, as well as antiseptic activity and microstructures characteristics were determined for these polymeric systems. Drug release behavior in the studied systems was also verified. The in vitro mucoadhesive capacity was determined with the formulations selected, using porcine oral mucous membrane like substrate.

Ketoprofen-loaded pomegranate seed oil nanoemulsion stabilized by pullulan: Selective antiglioma formulation for intravenous administration.

This study aimed to prepare pomegranate seed oil nanoemulsions containing ketoprofen using pullulan as a polymeric stabilizer, and to evaluate antitumor activity against in vitro glioma cells. Formulations were prepared by the spontaneous emulsification method and different concentrations of pullulan were tested. Nanoemulsions presented adequate droplet size, polydispersity index, zeta potential, pH, ketoprofen content and encapsulation efficiency. Nanoemulsions were able to delay the photodegradation profile of ketoprofen under UVC radiation, regardless of the concentration of pullulan. In vitro release study indicates that nanoemulsions were able to release approximately 95.0% of ketoprofen in 5h. Free ketoprofen and formulations were considered hemocompatible at 1 µg/mL, in a hemolysis study, for intravenous administration. In addition, a formulation containing the highest concentration of pullulan was tested against C6 cell line and demonstrated significant activity, and did not reduce fibroblasts viability. Thus, pullulan can be considered an interesting excipient to prepare nanostructured systems and nanoemulsion formulations can be considered promising alternatives for the treatment of glioma.

Polysaccharide nanoparticles for protein and Peptide delivery: exploring less-known materials.

Finding adequate carriers for protein and peptide delivery has become an urgent need, owing to the growing number of macromolecules identified as having therapeutic potential. Nanoparticles have emerged in the field as very promising vehicles and much work has been directed to testing the capacity of different materials to compose the matrix of these carriers. Natural materials and, specifically, polysaccharides have been taking the forefront of the challenge, because of several favoring properties that include the higher propensity to exhibit biodegradability and biocompatibility, and also the high structural flexibility. The majority of works found in the literature regarding polysaccharide nanoparticles uses very popular materials like chitosan or hyaluronic acid. This review is aimed at describing and exploring the potential of polysaccharides that are not so well known or that are less explored. For those, the main properties will be described, together with an overview of the reported applications as nanoparticle matrix materials.

Pullulan: an advantageous natural polysaccharide excipient to formulate tablets of alendronate-loaded microparticles

This work reports the preparation of tablets by direct compression of sodium alendronate-loaded microparticles, using pullulan as filler. The tableting properties of pullulan were compared with those of microcrystalline cellulose and lactose. Pullulan tablets showed low variations in average weight, thickness and drug content. Moreover, these tablets exhibited a higher hardness compared to the other excipients. In vitro release studies showed that only pullulan was capable to maintain gastroresistance and release properties of microparticles, due to its ability to protect particles against damage caused by compression force. Thus, pullulan was considered an advantageous excipient to prepare tableted microparticles.

Neste trabalho relata-se a preparação de comprimidos pela compressão direta de micropartículas contendo alendronato de sódio, utilizando o pullulan como diluente. As propriedades dos comprimidos de pullulan foram comparadas com as de comprimidos de celulose microcristalina e de lactose. Os comprimidos de pullulan mostraram baixa variação no peso médio, espessura e teor. Por outro lado, estes apresentaram altos valores de dureza comparados aos preparados com os outros excipientes. Através dos estudos de liberação in vitro pode-se observar que apenas o pullulan foi capaz de manter a gastrorresistência e as propriedades de liberação das micropartículas, o que se deve à sua capacidade de proteger as partículas do dano causado pela força de compressão. Dessa forma, o pullulan foi considerado um excipiente vantajoso para a preparação de comprimidos microparticulados.

Novel Pullulan-Eudragit® S100 blend microparticles for oral delivery of risedronate: formulation, in vitro evaluation and tableting of blend microparticles.

Polymer blends have been considered a promising strategy to tailor drug release. In order to achieve gastroresistance and controlled release, Pullulan, a polysaccharide, and Eudragit® S100, an enteric polymer were selected to prepare microparticles for oral delivery of risedronate, an antiresorptive drug associated with GI tract injuries. Blend microparticles were prepared by spray-drying technique at 3 Pullulan and Eudragit® S100 ratios (MP2:1, MP1:1 and MP1:2) and were characterized in terms of yield, particle size, encapsulation efficiency, morphology, moisture content, flowability and in vitro drug release profiles. Microparticles presented yields between 31 and 42%, encapsulation efficiencies close to 100%, moisture contents lower than 11%, particle size ranging from 2.9 to 4.8 µm and narrow distribution. In the gastric medium, MP1:2 showed the best gastroresistance profile. In the intestinal fluid, all samples were able to prolong drug release. MP1:2 was compressed into tablets with or without polyvinylpyrrolidone. Both tableted microparticles could be obtained with acceptable average weights, drug content close to 100%, sufficient hardness and low friability. In vitro studies showed that tablets maintained the gastroresistance observed for microparticles and were also able to prolong risedronate release. In conclusion, Pullulan/Eudragit® S100 microparticles are promising alternatives for the oral delivery of risedronate in the future.

Development of a buccal mucoadhesive film for fast dissolution: mathematical rationale, production and physicochemical characterization.

The validity of a mathematical rationale for preparation of a fast-dissolving buccal mucoadhesive was tested. A buccal mucoadhesive biopolymeric formulation has been developed having pullulan as the main component. The formulation was duly evaluated physicochemically, via assays for intrinsic viscosity (resulting in 71.61 cm3 g(-1)), differential scanning calorimetry analysis (resulting in a Tg = 63 °C), thermogravimetric analysis (244-341 °C), moisture content determinations (14%, w/w), dissolution timeframe (41.6 s), mucoadhesion force (40 kg/cm2), scanning electron microscopy analyses (critical ray under 1.0 µm), mechanic strength (tensile strength = 58 N/mm2, deformation = 4.4%). The mucoadhesive formulation exhibited important characteristics for a drug carrier, that is, a 6 cm2 area, a fast dissolution timeframe, an adequate mucoadhesivity, resistance to both oxygen and water vapor penetration, increased viscosity in solution (ranging from 33.2 cm3/g to 71.61 cm3/g), easy molding, suitable water solubility and transparency.